Article
Biochemistry & Molecular Biology
Christopher D. Putnam, Richard D. Kolodner
Summary: MutL family proteins have a conserved structure and mediate DNA mismatch repair. The function of the endonuclease active site and the role of the linker motif in regulating the activity are not well understood. This study proposes that the inhibitory cysteine in the FERC sequence sequesters the active site and suggests a functional interaction between the conserved linker motif and the FERC sequence.
Article
Biotechnology & Applied Microbiology
Martina Fiumara, Samuele Ferrari, Attya Omer-Javed, Stefano Beretta, Luisa Albano, Daniele Canarutto, Angelica Varesi, Chiara Gaddoni, Chiara Brombin, Federica Cugnata, Erika Zonari, Matteo Maria Naldini, Matteo Barcella, Bernhard Gentner, Ivan Merelli, Luigi Naldini
Summary: Base and prime editors have shown potential for precise genetic engineering, but their cellular responses and genotoxicity are not well understood. This study compared the efficiency, toxicity, and genotoxicity between base and prime editors and Cas9 in human hematopoietic cells. The findings suggest that these editors can induce harmful effects and genotoxicity, raising concerns for their clinical applications.
NATURE BIOTECHNOLOGY
(2023)
Review
Cell Biology
Adrian C. Bateman
Summary: DNA mismatch repair is a crucial physiological process for correcting mutations during DNA replication. Deficient MMR can increase tumor mutational burden and elevate the risk of cancer. Immunohistochemical assessment of MMR proteins to detect dMMR is valuable for screening inherited cancer syndromes like Lynch syndrome and predicting clinical responses to chemotherapy and immunotherapies. Identifying dMMR can also aid in diagnosing dysplasia in certain intestinal lesions.
Article
Oncology
Adar Yaacov, Oriya Vardi, Britny Blumenfeld, Avraham Greenberg, Dashiell J. Massey, Amnon Koren, Sheera Adar, Itamar Simon, Shai Rosenberg
Summary: This study systematically analyzed the mutational landscape of tumors and identified the association between mutational processes and replication timing. A novel method was developed to improve understanding of the etiology of mutational signatures.
Article
Biochemistry & Molecular Biology
Gloria X. Reyes, Anna Kolodziejczak, Lovely Jael Paul Solomon Devakumar, Takashi Kubota, Richard D. Kolodner, Christopher D. Putnam, Hans Hombauer
Summary: Mismatch repair (MMR) is crucial for maintaining genome stability by recognizing and excising DNA replication errors. In this study, overexpression of DNA ligase I (Cdc9) in Saccharomyces cerevisiae was found to interfere with MMR by prematurely ligating replication-associated nicks, leading to increased mutation rates and accumulation of MMR intermediates. This study established a general mechanism by which MMR targets newly synthesized DNA, preventing the accumulation of mutations that can contribute to the development of human cancer.
Review
Biochemistry & Molecular Biology
Jessica S. Williams, Thomas A. Kunkel
Summary: The focus of this review is on the incorporation of ribonucleotides into the eukaryotic nuclear genome during replication, their removal, and the consequences for genome stability and disease.
ANNUAL REVIEW OF BIOCHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Daniel Vaulot, Clarence Wei Hung Sim, Denise Ong, Bryan Teo, Charlie Biwer, Mahwash Jamy, Adriana Lopes dos Santos
Summary: Metabarcoding has become a popular method for studying microbial eukaryotic communities, with a newly-assembled database metaPR(2) providing processed 18S rRNA metabarcodes annotated with the PR2 reference sequence database. This database, containing over 4000 samples and 90,000 ASVs, is accessible through web-based interface and an R package, offering valuable resources for researchers studying protist diversity in various systems.
MOLECULAR ECOLOGY RESOURCES
(2022)
Article
Biochemistry & Molecular Biology
Mark Boltengagen, Daan Verhagen, Michael Roland Wolff, Elisa Oberbeckmann, Matthias Hanke, Ulrich Gerland, Philipp Korber, Felix Mueller-Planitz
Summary: In this study, the organization of nucleosomes in Saccharomyces cerevisiae was investigated using the Fiber-Seq technique. The results revealed deviations from the stereotypical nucleosome organization, including long linker DNAs between nucleosomes, missing nucleosomes in gene bodies, cell-to-cell heterogeneity in nucleosome occupancy, heterogeneous phasing of arrays, and irregular nucleosome spacing. These findings provide valuable information for understanding the chromatin structure and function.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Benjamin Morledge-Hampton, John J. Wyrick
Summary: The study developed a tool called mutperiod for quantifying mutational periodicities in nucleosomal DNA and comparing them across different genetic and cellular backgrounds. It was found that DNA mismatch repair contributes to nucleosome mutational periodicity, and the strength of this periodicity varies in different chromatin states.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Review
Biochemistry & Molecular Biology
Jiahui Zhu, Lexin Liu, Xiaodi Ma, Xinyu Cao, Yu Chen, Xiangping Qu, Ming Ji, Huijun Liu, Chi Liu, Xiaoqun Qin, Yang Xiang
Summary: The mortality rate of idiopathic pulmonary fibrosis (IPF) increases yearly due to ineffective treatment. Oxidative stress, especially DNA stimulation, plays a crucial role in pulmonary fibrosis. DNA damage is important in the initiation of IPF and DNA repair systems targeting damage are crucial for lung cell survival. However, existing research has not focused on the role of DNA damage and repair pathways in IPF.
Article
Biochemistry & Molecular Biology
Yuan Zhuang, Jiangle Liu, Hao Wu, Qingguo Zhu, Yongchang Yan, Haowei Meng, Peng R. Chen, Chengqi Yi
Summary: The HOPE method utilizes paired pegRNAs encoding the same edits to achieve high editing efficiency in human embryonic kidney and colorectal carcinoma cells, showing improved product purity compared to the original PE3 system. This enhanced tool has the potential to broaden both fundamental research and therapeutic applications of prime editing.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Medical Laboratory Technology
Liu Dong, Haoqin Jiang, Zhihua Kang, Ming Guan
Summary: Drugs targeting DNA repair have rapidly developed in cancer therapy, with numerous inhibitors being used in preclinical and clinical stages. Biomarkers are crucial for predicting chemotherapy response and DNA mismatch repair (MMR) pathway plays a significant role in cancer occurrence and development. This review provides a concise introduction of MMR genes and focuses on potential biomarkers for therapeutic response and resistance, aiming to clarify the controversial and contradictory results regarding the underlying mechanisms.
CLINICA CHIMICA ACTA
(2023)
Article
Microbiology
Min Jin, Jingjing Wu, Linli Shi, Bin Zhou, Fumei Shang, Xiaona Chang, Xiaochuan Dong, Shenghe Deng, Li Liu, Kailin Cai, Xiu Nie, Tao Zhang, Jun Fan, Hongli Liu
Summary: CRC patients with different MMR status have distinct gut bacterial community richness, compositions, and related metabolic pathways.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Genetics & Heredity
Hannah G. Daniels, Breanna G. Knicely, Anna Kristin Miller, Ana Thompson, Rina Plattner, Eva M. Goellner
Summary: The DNA mismatch repair pathway is crucial for genomic stability, and its defects can lead to genomic instability and increased mutation rates. This study demonstrates that tyrosine kinase inhibitors can reduce the expression of MLH1 protein, a critical component of the mismatch repair pathway. The study also reveals the role of ABL1 in regulating MLH1 through tyrosine phosphorylation and degradation. These findings contribute to our understanding of the regulation of the mismatch repair pathway and have important clinical implications for patient treatment.
FRONTIERS IN GENETICS
(2022)
Article
Multidisciplinary Sciences
Yo-Chuen Lin, Dazhen Liu, Arindam Chakraborty, Lyudmila Y. Kadyrova, You Jin Song, Qinyu Hao, Jaba Mitra, Rosaline Y. C. Hsu, Mariam K. Arif, Sneha Adusumilli, Ting-Wei Liao, Taekjip Ha, Farid A. Kadyrov, Kannanganattu V. Prasanth, Supriya G. Prasanth
Summary: This article investigates the role of Orc6, a component of the origin recognition complex (ORC), in DNA replication. The study discovers that Orc6 localizes at the replication fork and acts as an accessory factor of the mismatch repair (MMR) complex. In response to oxidative damage during the S phase, Orc6 promotes MMR complex assembly and activity, enabling efficient MMR. This suggests that hOrc6 plays a fundamental role in genome surveillance during DNA replication.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Genetics & Heredity
Marit A. E. van Bueren, Aniek Janssen
Summary: Eukaryotic nuclei rely on multiple repair pathways to accurately repair DNA damage, particularly in chromatin domains enriched for repetitive DNA sequences. Tailored repair mechanisms are necessary to maintain genome stability in these domains.
